Organ System Failure Research Articles

Identification of cuproptosis-related genes in septic shock based on bioinformatic analysis.

Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear. The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed. SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups. This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

Early identification of non-occlusive acute mesenteric ischemia

Acute mesenteric ischemia (AMI) is insidious in the early stage of the disease, and once ischemia reaches the late stage, irreversible intestinal necrosis and even multiple system organ failure occur, ultimately leading to death. Early diagnosis and intervention are the key to improving the outcome of AMI. Intensive care unit (ICU) patients mostly present with non-occlusive mesenteric ischemia (NOMI) due to hypoperfusion. This article reviews the high risk factors, clinical manifestations, biomarkers, and imaging examinations of AMI in order to provide ideas for clinicians in the early identification of this disease.

An initial exploratory clinical study and outcome assessment of gastrointestinal surgeries using advanced robotic-assisted techniques.

In addition to the Da Vinci surgical robot, domestic surgical robots are being developed rapidly. Chinese Toumai® laparoscopic surgical robot was approved for urological surgery in 2022.This study aims to systematically evaluate the safety and efficacy of the Toumai® robotic surgical system in performing complex gastrointestinal surgeries. This prospective, single-center, single-arm exploratory study was conducted at Gansu Provincial Hospital between June 2022 and October 2023, enrolling 12 patients undergoing gastrectomyand 9 patients undergoing colorectal resection. The primary endpoints are oncological outcomes and surgical success rates, while secondary endpoints encompassed intraoperative blood loss, operative duration, complication rates, system performance metrics, length of hospital stay, and postoperative pain levels. All patients successfully underwent robotic-assisted surgery with adequate oncological resection and favorable postoperative outcomes. There were no conversions to open or laparoscopic surgery, resulting in a 100% procedural success rate. The median docking time for radical gastrectomy was 17.50 (14.25, 21.50) minutes, with a median master-slave control time of 121.50 (105.50, 172.00) minutes, median intraoperative blood loss of 100.00 (50.00, 275.00) mL, and a median postoperative hospital stay of 9.00 (7.25, 10.75) days. For radical colorectal surgery, the median docking time was 22 (17.50, 30.50) minutes, the median master-slave control time was 68 (56.50, 119.00) minutes, with a median blood loss of 50 (50.00, 150.00) mL, and a median postoperative hospital stay of 7 (7.00, 10.00) days. No intraoperative organ injury, mortality, system failure, or severe postoperative complications were reported. These preliminary findings provide compelling evidence supporting the safety and efficacy of the Toumai® laparoscopic surgical robotic system in performing gastric and colorectal surgeries.

On-demand imidazolidinyl urea-based tissue-like, self-healable, and antibacterial hydrogels for infectious wound care

Bacterial wound infections are a growing challenge in healthcare, posing severe risks like systemic infection, organ failure, and sepsis, with projections predicting over 10 million deaths annually by 2050. Antibacterial hydrogels, with adaptable extracellular matrix-like features, are emerging as promising solutions for treating infectious wounds. However, the antibacterial properties of most of these hydrogels are largely attributed to extrinsic agents, and their mechanisms of action remain poorly understood. Herein we introduce for the first time, modified imidazolidinyl urea (IU) as the polymeric backbone for developing tissue-like antibacterial hydrogels. As-designed hydrogels behave tissue-like mechanical features, outstanding antifreeze behavior, and rapid self-healing capabilities. Molecular dynamics (MD) simulation and density functional theory (DFT) calculation were employed to well-understand the extent of H-bonding and metal-ligand coordination to finetune hydrogels’ properties. In vitro studies suggest good biocompatibility of hydrogels against mouse fibroblasts & human skin, lung, and red blood cells, with potential wound healing capacity. Additionally, the hydrogels exhibit good 3D printability and remarkable antibacterial activity, attributed to concentration dependent ROS generation, oxidative stress induction, and subsequent disruption of bacterial membrane. On top of that, in vitro biofilm studies confirmed that developed hydrogels are effective in preventing biofilm formation. Therefore, these tissue-mimetic hydrogels present a promising and effective platform for accelerating wound healing while simultaneously controlling bacterial infections, offering hope for the future of wound care.

Machine learning−derived multivariable predictors of postcardiotomy cardiogenic shock in high-risk cardiac surgery patients

ObjectiveTo develop a model for preoperatively predicting postcardiotomy cardiogenic shock (PCCS) in patients with poor left ventricular (LV) function undergoing cardiac surgery. MethodsFrom the Society of Thoracic Surgeons Adult Cardiac Database, 11,493 patients with LV ejection fraction ≤35% underwent isolated on-pump surgery from 2018 through 2019, of whom 3428 experienced PCCS. In total, 68 preoperative clinical variables were considered in machine-learning algorithms trained and optimized using scikit-learn software. ResultsCompared with patients with ideal recovery, those that did were younger (65 vs 67 years), more likely female, Black, with low LV ejection fraction (26.5 vs 28.9%), previous myocardial infarction, chronic lung disease, diabetes, reoperation, or advanced heart failure. Among those with PCCS versus ideal recovery, operative mortality was 27% (925/3428) versus 0.1% (5/8065). PCCS occurred more often after coronary artery bypass grafting with concomitant mitral valve repair or after longer perfusion and clamp times. Reliable preoperative PCCS predictors were more advanced cardiac, liver, and renal failure; frailty; and greater white cell count. Out of sample test set receiver operating curve achieved an area under the curve of 0.74 with acceptable calibration Hosmer-Lemeshow statistic χ2 = 1.33, P = .25. ConclusionsIn patients with severe LV dysfunction undergoing cardiac surgery, risk of PCCS is elevated by preoperative failure of other organ systems and complexity of the planned operation that prolongs myocardial ischemia and cardiopulmonary bypass. This risk calculator could serve as an important tool to preoperatively identify patients in need of advanced levels of support.

Unraveling the immune response of the spleen in sepsis using green-synthesized silver nanoparticles from pomegranate peel extracts.

Sepsis is a serious disease characterized by an inappropriate host response to infection, resulting in widespread inflammation and systemic organ failure. The aim of this research is to investigate the possibility of pomegranate peel-derived silver nanoparticles (PGNP) as a potential alternative therapy for sepsis. Characterization using transmission electron microscopy revealed 10-30 nm spherical nanoparticles. In a rat model of sepsis, PGNP treatment improved spleen health, histology, and immune response as compared with septic rats. In rats treated with PGNP during sepsis, significant alterations in oxidative stress markers (p < .01) were observed. These included elevated levels of glutathione (0.63 ± 0.08 mmol/mg protein), reduced concentrations of nitric oxide (8.7 ± 0.8 μ mol/mg protein) and malondialdehyde (2.2 ± 0.3 nmol/mg protein), as well as increased activity of superoxide dismutase (159 ± 33 U/mg protein). Following PGNP administration, gene expression analysis revealed a decrease in spleen IL-1β, IL-6, and TNF-α, highlighting its anti-inflammatory potential. Furthermore, PGNP effectively controlled apoptosis-related genes (Bax, Bcl-2, and Casp3), indicating its role in cellular survival pathways. This study sheds light on the immunological regulation of the spleen during sepsis using PGNP, demonstrating its potential as a new effective treatment approach. The study emphasizes the necessity of continuing to investigate and develop alternative medicines, particularly in light of antibiotic resistance and the global impact of sepsis. RESEARCH HIGHLIGHTS: The study explored the potential medicinal benefits of pomegranate peel-derived silver nanoparticles (PGNP) in the treatment of sepsis. PGNP suppressed pro-inflammatory cytokines and enhanced the immune response. The study recommends PGNP as a viable substitute treatment.

Comprehensive management of a child with X-linked lymphoproliferative disease undergoing stem cell transplantation: a case report

An uncommon immunodeficiency disease known as X-linked lymphoproliferative disease (XLP) has been associated with severe immunological dysfunction and a high susceptibility to Epstein-Barr virus (EBV) infections. This case report describes a four-year-old boy who had X-linked lymphoproliferative illness and died from multiple system organ failure (MSOF) after receiving treatment with a haploidentical hematopoietic stem cell transplant (halo-HSCT). While providing care in such circumstances, rational-based care, prompt identification, primary nursing care, health education, and emotional assistance for parents of individuals with X-linked lymphoproliferative diseases are vital.

Barriers and facilitators when seeking healthcare for septic children in Ghana: a single-centre qualitative study of patient caregivers and emergency department clinicians

Background/purposeSepsis is a leading cause of morbidity, mortality and healthcare utilisation for children worldwide, particularly in resource-limited regions. In Kumasi, Ghana, organ system failure and mortality in children who present...

Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management.

Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.

High Levels of Triggering Receptor Expressed in Myeloid Cells-Like Transcript-1 Positive, but Not Glycoprotein 1b+, Microparticles Are Associated With Poor Outcomes in Acute Respiratory Distress Syndrome.

To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS). Retrospective cohort study. ARDS Network clinical trials. A total of 564 patients were diagnosed with ARDS. None. Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors. Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.

Acute Kidney Injury in ARDS: Insights into Physiology and Pathology

Abstract: Acute kidney injury is a common problem in the critically ill patient. It is often part of the multi system organ failure syndrome where other organs such as the lungs are involved. In the critically ill patient, primary pathology in one organ can affect other organs, and systemic illness can affect both at the same time. In this review article, we closely examine the definition and stages of dysfunction in lungs and kidneys and the relationship between the physiology and pathology of these two organs as they interact and affect each other in the critically ill patient. We also seek to understand the effects common intensive care units interventions have on both those organs, with a special emphasis on external life support devices such as mechanical ventilation, dialysis and extracorporeal membranous oxygenation.

Sitagliptin ameliorates L-arginine-induced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress.

Acute pancreatitis (AP) is an inflammatory condition that resolves spontaneously, but occasionally, develops into systemic inflammation, organ failure and mortality. Oxidative stress and activation of inflammatory pathways represent major players in AP pathogenesis. Current management of AP relies on attenuating injuries to the pancreas and putting the inflammatory process under control. In this study, we investigated the role of sitagliptin in modulating L-arginine-induced AP in rats. Swiss rats were subdivided into a healthy control group, AP group (a single dose of L-arginine 250mg/100g, intraperitoneal), and sitagliptin + L-arginine-treated group (10mg sitagliptin/kg body weight/day, orally). Sitagliptin treatment started 1hour after L-arginine injection and continued for 3days. Biochemical and histopathological investigations were performed on serum and tissue samples collected from test animals. L-arginine increased pancreatic meyloperoxidase and serum amylase- and lipase activities and serum levels of TNF-α, LT-α, IFN-γ, IL-1α/β, IL-6, IL-10, IL-12, and IL-15. AP animals showed elevated MDA and NO and decreased GSH and serum calcium levels. Histopathological changes were observed by H&E staining. Sitagliptin treatment significantly ameliorated these biochemical and histological changes diminishing the signs of AP. Sitagliptin treatment was effective in ameliorating L-arginine-induced AP which can be regarded to its anti-inflammatory and antioxidant effect.

#557 Seraph® 100 affinity blood cartridge as a potential adjunctive blood purification strategy for S. aureus-induced septic shock

Abstract Background and Aims S. aureus infections, particularly methicillin-resistant strains, can induce severe conditions, provoking an overwhelming immune response and contributing to systemic inflammation and organ failure. Effective antibiotic therapy and meticulous supportive care are crucial in the ICU to manage S. aureus-induced septic shock. In this context, blood purification strategies aim to target the microorganism and associated toxins, contributing to the systemic inflammatory cascade. The objective of this in-vitro study was to analyze the potential removal, through adsorption, by the Seraph100 Affinity Blood Cartridge (S100ABC) against S. aureus. Subsequently, the study assessed whether the adsorptive capabilities toward bacteria were maintained, and if so, whether the bacteria retained its bactericidal activity. Method The study employed an in vitro model of hemoadsorption to characterize the adsorption performed by the S100ABC on a circulating bacterial load inoculated in blood. A volume of 150 ml of blood served as a negative control (CTR-). The remaining 650 mL were enriched with a concentration of S. aureus bacteria equal to 1×106 and incubated for 4 h at 37°C. At 4 h, the blood was divided into 2 glass bowls and stirred at 37°C: 500 mL were circulated at a speed of 120 mL/min via a dedicated test platform (Galileo) with Seraph100, while another 150 mL was stirred and used as a positive control (CTR+). The experiment was performed twice. Samples were taken from circulating blood and the two controls for blood cultures and placement on CNA agar. Results This study demonstrated that the S100ABC reduces the circulating bacterial load (from 1x106 at T0 to 0.25x106 at T6 h), leading to the adsorption of bacteria onto the cartridge. Bacteria were found adhering to the beads contained in the cartridge. Conclusion Our preliminary data show that the S100ABC effectively reduces the circulating bacterial load. The S100ABC could be an adjunct sorbent for reducing S. aureus in human blood, supporting antibiotic therapy in patients with S. aureus-induced septic shock.

Acute Respiratory Failure in Autoimmune Rheumatic Diseases: A Review.

This review examines respiratory complications in autoimmune rheumatic diseases within intensive care units (ICUs). The respiratory system, primarily affected in diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma, often leads to respiratory failure. Common manifestations include alveolar hemorrhage, interstitial fibrosis, and acute respiratory distress syndrome. Early recognition and treatment of non-malignant conditions are crucial to prevent rapid disease progression, with ICU mortality rates ranging from 30% to 60%. Delayed immunosuppressive or antimicrobial therapy may result in organ system failure. Collaboration with rheumatic specialists is vital for accurate diagnosis and immediate intervention. Mortality rates for rheumatic diseases in the ICU surpass those of other conditions, underscoring the need for specialized care and proactive management. The review emphasizes comprehensive assessments, distinguishing disease-related complications from underlying issues, and the importance of vigilant monitoring to enhance patient outcomes.

The Impact of COVID-19 on Mortality and Clinical Characteristics in Hospitalized Patients With Peripheral Artery Disease in the Year 2020 in Germany.

The COVID-19 pandemic developed its full destructive capacity in 2020. This retrospective study aimed to examine the effects of COVID-19 on the mortality and the clinical characteristics in PAD patients with COVID-19 compared to PAD patients without COVID-19. Data derived from a German nationwide register of the year 2020 which encompassed all hospitalized patients with PAD (n = 173.075); N = 2553 also suffered from a COVID-19 infection and had significantly higher mortality rates of 11.2%. PAD + COVID-19 patients presented more clinical complications like major amputations (11.59%), myocardial infarction (2.08%), cardiogenic shock (2.98%), chronic kidney failure with GFR<= 15mL/min (5.33%) and prolonged ventilation time >48 h (3.37%). Rates of pulmonary thromboembolism (0.24%), myocardial infarction (2.08%), and stroke (1.02%) were low in patients with PAD + COVID-19. Adjusted regression analyses for risk differences revealed possible causes of higher mortality rates, such as prolonged ventilation time, pneumonia, major amputations, multiple organ system failure, and length of hospital stay in patients with severe PAD (Rutherford 5-6) + COVID-19. Pneumonia and major amputations were associated with high mortality rates in PAD + COVID-19 in 2020. However, we could not detect a relevant influence of pulmonary thromboembolism, myocardial infarction or stroke on higher death rates of PAD + COVID-19.

Primary and specialty palliative care utilization at a regional Burn center.

There is little research informing appropriate specialty palliative care consultation over primary palliative care practice, or the ability of the burn surgeon to perform skills such as effective goals of care discussions. We sought to characterize patterns of palliative care utilization and hypothesized that greater modified Baux (mBaux) and systemic organ failure assessment (SOFA) scores would correlate with increased specialty palliative involvement but have no relationship with primary palliative involvement. A retrospective chart review was conducted at a regional burn center between 2020-2021 including patients admitted with burns or inhalation injury and a mBaux score over 60, detailing circumstances of palliative consultation and goals of care discussions. 163 patients met criteria. Odds of specialty palliative consultation increased by 3.9% for each additional mBaux score point and 23.3% for every SOFA score point. The odds of a goals of care discussion by a burn surgeon increased by 3.5% for each mBaux score point and 23.9% for each SOFA score point. Those receiving palliative consultation tended to have greater burn surface area, graft complications, code status changes, and more goals of care discussions by any provider at admission; there was no difference in symptom control or hospital length of stay. Higher mBaux and SOFA scores correlate with increased odds of both specialty and primary palliative involvement in our cohort. There is bias in diverting both primary and specialty palliative care resources toward acutely ill patients and those with less immediate projected mortality may need additional attention.

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

Effect of dysnatremia and dysglycemia on outcomes among surgical intensive care unit patients

Objectives: The objectives of this study were to evaluate the relationships between serum sodium and glucose concentrations and outcomes among patients admitted to the surgical intensive care unit. Materials and Methods: Patient records admitted to the surgical intensive care unit (SICU) between July 2020 and December 2020 were used in the study. Data included in the analysis were patient age, gender, comorbidities, surgical intervention, diagnosis of sepsis, sequential organ system failure scores, serum sodium concentrations, serum glucose concentrations, and surgical intensive care unit outcomes (discharged vs. deceased). A univariate logistic regression analysis was used to determine significant risk factors for mortality during a surgical intensive care unit stay. Results: A total of 194 patients with a mean age of 60±16 years were admitted to the SICU during the study period. Twenty-three percent of the patients were found to have sepsis with 18% mortality. Serum sodium and glucose concentrations were significantly higher (P-value ≤0.05) at all-time points in deceased patients compared to those who were discharged from the SICU. Conclusion: The results of the study indicate that serum sodium and glucose concentrations could be used as independent predictors of mortality in surgical intensive care unit patients with sepsis. However, further clinical trials are warranted before this application could be recommended in surgical intensive care units.

Rare neurologic sequelae: A case report of toxic metabolic encephalopathy caused by carbamazepine-induced hypovolemic hyponatremia

Metabolic or secondary encephalopathies originate from non-cerebral organ system failures, often with multifactorial origins. Toxic-metabolic encephalopathy (TME) results from acute cerebral dysfunction due to metabolic disruptions, including drug effects. TME leads to altered consciousness, from delirium to coma, necessitating intensive care and mechanical ventilation. This study delves into TME, a reversible brain pathology triggered by extracerebral factors, notably drug-induced disturbances. Clinical presentation involves nonspecific altered consciousness, sometimes with asterixis or myoclonus. Carbamazepine (CBZ), a common antiepileptic medication, is linked to hyponatremia, defined by serum sodium levels below 135 mmol/l. The complexity of AED-induced hyponatremia is explored through a comprehensive patient analysis, revealing an array of symptoms including altered mentality, seizures, respiratory distress, and even coma or death. The case study dissects a patient's experience with toxic-metabolic encephalopathy secondary to CBZ-induced hypovolemic hyponatremia. This underscores the need for vigilant monitoring and management of adverse drug reactions, spotlighting the intricate interplay of drug-induced metabolic encephalopathies within clinical practice. The study reinforces the importance of awareness and tailored management strategies to enhance treatment outcomes for individuals with epilepsy.

Effect of plasma exchange with albumin replacement on albumin functionality and organ dysfunction in acute-on-chronic liver failure

Effective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Ten adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE). Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n= 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6mg/ml to 18.9±1.7mg/ml; p= 0.003), fatty acid-binding capacity (8.2±1.4μM to 3.1±1.5μM; p= 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5mg/ml to 14.6±1.6mg/ml; p= 0.001). Native albumin levels were increased throughout day 1-11PE-A5% sessions (6.5±1.0mg/ml to 10.2±1.4mg/ml; p= 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none). PE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Acute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF. NCT01201720. 2010-021360-15.